The proposal is a continuation of the work of this laboratory on neurohormonal regulation of gastric activity. Four subprojects are proposed: 1. The effect of chronic administration of large doses of gastrin, cholecystokinin, secretin, and glucagon on the mass of the gastric mucosa and on the maximal capacity to secrete acid in rats with gastric fistulas. The aim is to determine the factors that regulate growth of gastric mucosa. 2. Structure-activity relations of synthetic peptides related to caerulein in relation to ability to inhibit gastrin stimulated gastric acid secretion in dogs with Heidenhain pouches. The aim is to define the minimal structural requirements for inhibition and relate these to minimal structural requirements for other kinds of biological activity. 3. Comparison of truncal and selective vagotomy in man in regard to inhibition of gastric acid secretion by acid or fat instilled into the duodenum. The aim is to determine the effect of vagal denervation of the small intestine on release of gastric inhibitors. 4. Study of arterio-venous differences in plasma gastrin across various organs. The aim is to determine the sites and mechanisms of inactivation of gastrin.